Penicillins and cephalosporins are β-lactam antibiotics that are widely and frequently used in the clinic. However, the acquisition of resistance to β-lactam antibiotics by various pathogens has had a damaging effect on maintaining the effective treatment of bacterial infections. The most significant known mechanism related to the acquisition of bacterial resistance is the production of class A, C, and D β-lactamases having a serine residue at the active center. These enzymes decompose the β-lactam antibiotic, resulting in the loss of the antimicrobial activities. Class A β-lactamases preferentially hydrolyze penicillins while class C β-lactamases have a substrate profile favoring cephalosporins.
Commercially available β-lactamase inhibitors, e.g., clavulanic acid, sulbactam, and tazobactam, are known inhibitors effective mainly against class A β-lactamase producing bacteria, and are used as a mixture with a β-lactam antibiotic. However, many hundreds or more of β-lactamases have been reported to date, including those from resistant bacteria which produce class A KPC-2 β-lactamase decomposing even carbapenems.
In recent years, infectious diseases caused by the above-mentioned resistant bacteria as pathogenic bacteria are found not only in severe infectious disease but also occasionally in community-acquired infectious disease. The currently available antibiotics and β-lactamase inhibitors are progressively becoming ineffective against the incessantly increasing activities of constantly mutating bacterial β-lactamases and as such novel β-lactamase inhibitors and other antibacterial agents are required for the demanding treatment of infectious diseases caused by resistant bacteria.